Ribociclib Plus Endocrine Therapy Demonstrates PFS Advantage in HR+/HER2– Advanced Breast Cancer

Yen-Shen Lu, MD, PhD

Frontline treatment with ribociclib (Kisqali) in combination with endocrine therapy displayed a significant progression-free survival (PFS) benefit with superior tolerability vs combination chemotherapy in patients with clinically aggressive hormone receptor–positive, HER2-negative advanced breast cancer, according to findings from the phase 2 RIGHT Choice trial (NCT03839823) published in the Journal of Clinical Oncology.

At a median follow-up of 37.0 months, patients who received ribociclib plus endocrine therapy (n = 112) achieved a median PFS of 21.8 months (95% CI, 17.4-26.7) compared with 12.8 months (95% CI, 10.1-18.4) among patients treated with combination chemotherapy (n = 110; HR, 0.61; 95% CI, 0.43-0.87; P = .003). Moreover, the overall response rates (ORRs) were 66.1% (95% CI, 56.5%-74.7%) vs 61.8% (95% CI, 52.1%-70.9%), respectively, and the median time to response was 4.9 months vs 3.2 months, respectively (HR, 0.76; 95% CI, 0.55-1.06).

“The data show PFS superiority with ribociclib plus endocrine therapy over combination chemotherapy, with similar response rates, lower symptomatic AE [adverse effect] rates, and fewer discontinuations due to treatment-related AEs,” Yen-Shen Lu, MD, PhD, the chief of the Division of Medical Oncology in the Department of Oncology, National Taiwan University Hospital, as well as a clinical professor in the Department of Internal Medicine, National Taiwan University College of Medicine in Taipei, and coauthors wrote. “Thus, ribociclib plus endocrine therapy could be considered a first-line treatment option in this patient population.”

RIGHT Choice was an open-label study examining ribociclib plus endocrine therapy in patients with progesterone or estrogen receptor–positive, HER2-negative locoregionally recurrent or metastatic breast cancer not amenable to surgery that was conducted in 13 countries. The trial included pre/perimenopausal women 18 to 59 years old with an ECOG performance status of 2 or less and measurable disease per RECIST v1.1 criteria. Patients who received neoadjuvant or adjuvant treatment for breast cancer were eligible, as were those who received adjuvant aromatase inhibitor therapy if the subsequent treatment-free interval exceeded 12 months.

Eligible patients were randomly assigned 1:1 to receive oral ribociclib 600 mg daily on a 3-weeks-on, 1-week-off dosing schedule plus endocrine therapy consisting of letrozole 2.5 mg or anastrozole 1 mg orally via a continuous daily schedule with subcutaneous goserelin 3.6 mg on day 1 of each 28-day cycle; or investigator’s choice of combination chemotherapy. The available chemotherapy regimens consisted of docetaxel plus capecitabine (Xeloda), paclitaxel plus gemcitabine, or capecitabine plus vinorelbine. If a patient was forced to discontinue one chemotherapy due to AEs, they were permitted to continue monotherapy with the other agent.

The primary end point was locally assessed PFS. Secondary end points included time to treatment failure, 3-month treatment failure rate, ORR, clinical benefit rate (CBR), time to response, overall survival (OS), health-related quality of life, and safety.

The baseline patient characteristics were well balanced between the 2 arms; the median age was 44.0 years (range, 26-58) vs 43.0 years (range, 26-55) in the ribociclib and chemotherapy arms, respectively. Most patients in both arms were Asian (53.6% vs 52.7%), had histological grade II tumors (58.9% vs 55.5%), had an ECOG performance status of 1 (56.3% vs 56.4%), had de novo disease (62.5% vs 66.4%), and were progesterone receptor positive (88.4% vs 92.7%). In terms of metastatic sites, patients had 1 (17.0% vs 10.0%), 2 (25.9% vs 35.5%), or at least 3 (57.1% vs 54.5%).

Additional findings from RIGHT Choice showed that the CBR in the investigational arm was 81.3% (95% CI, 72.8%-88.0%); patients had complete response (CR), partial response (PR), stable disease, and progressive disease rates of 6.3%, 59.8%, 24.1%, and 8.0%, respectively. In the control arm, the CBR was 74.5% (95% CI, 65.4%-82.4%); the CR, PR, stable disease, and progressive disease rates were 2.7%, 59.1%, 18.2%, and 5.5%, respectively.

The 12- and 24-month PFS rates were 68.9% (95% CI, 59.3%-76.7%) and 46.5% (95% CI, 36.4%-56.0%), respectively, in the ribociclib arm, compared with 54.5% (95% CI, 43.7%-64.0%) and 23.6% (95% CI, 14.2%-34.4%), respectively, in the chemotherapy arm. The median OS was not reached (NR) in either the ribociclib (95% CI, 38.6-NR) or the chemotherapy (95% CI, 30.8-NR) arm (HR, 0.92, 95% CI, 0.56-1.52). The 12-, 18-, 24- and 30-month OS rates were 87.9%, 85.1%, 77.3%, and 66.6% in the ribociclib arm, respectively, vs 92.5%, 86.5%, 73.7%, and 64.6% in the chemotherapy arm, respectively.

In terms of safety, all patients in both the ribociclib and chemotherapy arms experienced at least 1 any-grade AE; grade 3 or 4 AEs occurred at rates of 79.5% and 73.0%, respectively. The most common grade 3 or 4 AEs included neutropenia (59.8% vs 36.0%) and leukopenia (25.0% vs 8.0%). Patients discontinued study treatment due to treatment-related AEs at rates of 6.3% vs 27.0%, respectively; 5 deaths occurred in the investigational arm during the 30 days following the conclusion of study treatment due to disease progression; no on-treatment deaths were reported in the chemotherapy arm.

“This final analysis of the RIGHT Choice trial showed a clinically meaningful, statistically significant PFS benefit with first-line ribociclib plus endocrine therapy over combination chemotherapy in premenopausal women with clinically aggressive hormone receptor–positive, HER2-negative advanced breast cancer in which combination chemotherapy is typically is used to achieve a rapid tumor response. This PFS benefit was observed in most subgroups,” study authors wrote in conclusion. “The OS data, although immature at final database lock, showed a similar survival trend for both arms, suggesting there is likely no meaningful difference in survival benefit with combination chemotherapy vs ribociclib plus endocrine therapy.”

Reference

Lu YS, Bin Mohd Mahidin EI, Azim H, et al. Final results of RIGHT Choice: ribociclib plus endocrine therapy vs combination chemotherapy in premenopausal women with clinically aggressive HR+/HER2− advanced breast cancer. J Clin Oncol. Published online May 21, 2024. doi:10.1200/JCO.24.00144